SCF ubiquitin ligase-targeted therapies.
SCF ubiquitin ligase-targeted therapies.
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DOI：
10.1038/nrd4432
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发表时间：
2014-12
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最近在治疗癌症的蛋白酶体抑制剂的临床成功突出了这种蛋白质降解系统的治疗潜力。蛋白酶体抑制剂可以阻止许多蛋白质的降解，因此可以通过抑制泛素-蛋白酶体系统中针对特定蛋白质亚群进行降解的组分来提高特异性。F-box蛋白是SKP1-CUL1-F-box蛋白（SCF）泛素连接酶复合物的底物靶向亚基。通过大量不同底物的降解，SCF泛素连接酶在细胞和生物体水平上控制着大量的过程，它们的失调与许多病理有关。SCF连接酶的特点是对其底物具有高特异性，因此它们代表了有希望的药物靶点。然而，潜在的治疗操作的SCF复合物仍然是一个不发达的领域。这篇综述将探索和讨论靶向scf介导的生物学治疗人类疾病的潜在策略。
The recent clinical successes of inhibitors of the proteasome for the treatment of cancer have highlighted the therapeutic potential of this protein degradation system. Proteasome inhibitors prevent the degradation of numerous proteins, so increased specificity could be achieved by inhibiting the components of the ubiquitin-proteasome system that target specific subsets of proteins for degradation. F-box proteins are the substrate-targeting subunits of SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complexes. Through the degradation of a plethora of diverse substrates, SCF ubiquitin ligases control a large number of processes at the cellular and organismal levels, and their misregulation is implicated in many pathologies. SCF ligases are characterized by a high specificity for their substrates, so they represent promising drug targets. However, the potential for therapeutic manipulation of SCF complexes remains an underdeveloped area. This review will explore and discuss potential strategies to target SCF-mediated biology to treat human diseases.